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Series GSE245668 Query DataSets for GSE245668
Status Public on Feb 28, 2024
Title SOX17 initiates an immune evasion program in early colorectal cancers [RNAseq_230707Yil]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In addition to accumulation of step-wise genetic mutations, epigenetic alterations play critical roles in the evolution of colon cancers. However, distinct mutational patterns and patient backgrounds render it challenging to distinguish driver epigenetic alterations from passenger epigenetic alterations. To address this, we combined the colon cancer organoid orthotopic transplantation approach with comprehensive epigenomic and transcriptomic analyses. We found that an in vivo environment induces epigenetic alterations with fetal intestinal features that converge on SOX17, a transcription factor that is required for endoderm development. Surprisingly, SOX17 knockout leads to tumour rejection in immunocompetent mice, but not in immunodeficient mice, by turning immune cold tumours into hot with robust infiltration of activated CD8+ T cells. Mechanistically, SOX17 suppresses Ifngr1-mediated MHC-I expression to evade CD8+ T cell-mediated tumour cell killing. At the tumour initiation, SOX17 expression is induced by APC loss, and SOX17 facilitates the production of LGR5- cells with low MHC-I expression to evade immune surveillance. Together, our result reveals that SOX17 is a master transcriptional factor that induces in vivo epigenetic reprograming of tumours, which provides fundamental understanding of how an immune evasion program is initiated at the early stages of colon cancer development.
 
Overall design We performed RNA-seq in naïve AKP organoids, bulk primary tumours, and flow cytometry-sorted tdTomato+ tumour cells from primary tumours. Furthermore, we employed Villin-CreERT2; Apc f/f; Kras LSL-G12D; P53 f/f; Rosa LSL-tdTomato (AKPVT) mice to generate autochthonous tumours by colonoscopy-guided 4-OH-Tamoxifen injection into the colonic mucosa. We perfomed RNA-seq in these endogenous AKPVT tumours and normal colonic crypts.
 
Contributor(s) Goto N, Goto S, Agudo J, Yilmaz O
Citation(s) 38418875
Submission date Oct 18, 2023
Last update date Apr 12, 2024
Contact name Norihiro Goto
E-mail(s) ngoto@mit.edu
Organization name Massachusetts Institute of Technology
Department Department of Biology
Lab Yilmaz lab
Street address 500 Main Street, Building 76
City Cambridge
State/province MA
ZIP/Postal code 02139-4307
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (24)
GSM7846687 Naïve_AKP_organoid_replicate1 [Naive.d9616]
GSM7846688 Naïve_AKP_organoid_replicate2 [Naive.d9617]
GSM7846689 Naïve_AKP_organoid_replicate3 [Naive.d9618]
This SubSeries is part of SuperSeries:
GSE222713 SOX17 initiates an immune evasion program in early colorectal cancers.
Relations
BioProject PRJNA1029549

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE245668_ngoto_230707Yil_intCt.txt.gz 991.3 Kb (ftp)(http) TXT
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Raw data are available in SRA

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